The objective of this program is the development of chromatographic-mass spectrometric methodology for the analysis of compounds of biological interest. Our work has focussed on areas of instrumentation development as well as the basic chromatographic/mass spectrometric properties of biologically relevant compounds or their derivatives. In the area of applications of chromatography and mass spectrometry to the analysis of CNS-active and other drugs and their metabolites, we have investigated the properties of N-n-propylnorapomorphine (NPA) and procarbazine and their metabolites. We have demonstrated the feasibility of quantitating NPA at the picogram level in urine and plasma. We have also applied mass spectrometry to study the in vivo metabolism of procarbazine in rats. In the area of steroid analysis by GC/MS we have been investigating the aromatization of the A-ring in steroidal epoxides as a result of the flash vaporization in the injector of the GC during GC/MS analysis. We have now developed micropacked columns (40 micrometer particles, 1 mm i.d. columns) which can yield 10,000 plates/meter at injector pressures of approximately 12 atmospheres. The use of these columns in on-line GC/MS is being investigated. For the area of HPLC/MS we have demonstrated the compatibility of reversed phase HPLC with MS using ion pair derivatives.